dbSNP rs1468030868: PEX5L:p.Met193Val (chr3-179875406-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_001256756.2(PEX5L):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PEX5L
NM_001256756.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Publications

0 publications found

Variant links:

Genes affected

PEX5L (HGNC:30024): (peroxisomal biogenesis factor 5 like) Enables peroxisome matrix targeting signal-1 binding activity and small GTPase binding activity. Predicted to be involved in protein import into peroxisome matrix, docking and regulation of cAMP-mediated signaling. Predicted to act upstream of or within maintenance of protein location and regulation of membrane potential. Located in cytosol. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

PEX5L links:

PEX5L-AS1 (HGNC:41251): (PEX5L antisense RNA 1)

PEX5L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 91 codons. Genomic position: 179819952. Lost 0.208 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256756.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX5L	NM_016559.3	MANE Select	c.577A>G	p.Met193Val	missense	Exon 6 of 15	NP_057643.1	Q8IYB4-1
PEX5L	NM_001256756.2		c.1A>G	p.Met1?	start_lost	Exon 5 of 14	NP_001243685.1	Q8IYB4-8
PEX5L	NM_001349399.2		c.1A>G	p.Met1?	start_lost	Exon 4 of 13	NP_001336328.1	Q8IYB4-8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX5L	ENST00000467460.6	TSL:1 MANE Select	c.577A>G	p.Met193Val	missense	Exon 6 of 15	ENSP00000419975.1	Q8IYB4-1
PEX5L	ENST00000263962.12	TSL:1	c.571A>G	p.Met191Val	missense	Exon 6 of 15	ENSP00000263962.8	Q8IYB4-2
PEX5L	ENST00000485199.5	TSL:1	c.472A>G	p.Met158Val	missense	Exon 5 of 14	ENSP00000418440.1	Q8IYB4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251470

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111126

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.12

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.055

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.32

REVEL

Benign

0.22

Sift

Benign

0.32

Sift4G

Benign

0.52

Polyphen

0.0010

Vest4

0.22

MutPred

0.22

Gain of glycosylation at S198 (P = 0.0055)

MVP

0.55

MPC

0.41

ClinPred

0.059

GERP RS

2.2

Varity_R

0.098

gMVP

0.067

Mutation Taster

=38/162

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over